Evidence for tangeretin O-demethylation by rat and human liver microsomes

• Published in: Xenobiotica
• Main Authors: Canivenc Lavier, Marie-Chantal, Brunold, C., Siess, Marie-Hélène, Suschetet, Marc
• Other Authors: UR 0938 Unité de Toxicologie nutritionnelle, Institut National de la Recherche Agronomique (INRA), UR 0938 DIJ TOX NUTRITIONN Unité de Toxicologie nutritionnelle
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 1993
• Subjects: Rat; Pharmacologie; Biologie animale; human; liver function tests; enzymic activity; 2-phenyl-2-ene-benzopyran-4-one compounds; rattus rattus; homme; tangeritine; foie; métabolisme; déméthylation; activité enzymatique; inhibition; flavone; cytochrome p450; microsome; [SDV]Life Sciences [q-bio]; Rattus rattus
• Online Access: https://hal.archives-ouvertes.fr/hal-01856403; https://doi.org/10.3109/00498259309059379

1. Tangeretin, a polymethoxylated flavone, was studied as a substrate for cytochrome P450-catalysed demethylation reactions by rat and human liver microsomes. Evidence has been presented for the production of formaldehyde in the presence of tangeretin and NAD(P)H. Kinetic studies showed a Km value for tangeretin of about 18 μM in both species. 2. The reaction was inhibited by CO, piperonyl butoxide, 7,8-benzoflavone, propyl gallate, aminobenzothiazole and metyrapone. 3. Rats pretreated with classical cytochrome P450 inducers (Aroclor 1254, 3-methylcholanthrene, phenobarbital, dexamethasone and ciprofibrate) or with flavonoids (flavone, flavanone, quercetin and tangeretin) resulted in increased microsomal demethylation of tangeretin after 3-methylcholanthrene and flavone only. Tangeretin did not enhance its own metabolism. 4. Tangeretin interacted with the oxidized form of cytochrome P450 to produce a reverse type I spectrum. 5. Results indicate that tangeretin is metabolized in liver microsomes by an O-demethylation reaction involving cytochrome P450.